Abstract: Nonnative residual interactions have attracted increasing attention in recent
protein folding researches. Experimental and theoretical investigations had
been set out to catch nonnative contacts that might dominate key events in
protein folding. However, energetic frustrations caused by nonnative
inter-residue interactions are not systematically characterized, due to the
complicated folding mechanism. Recently, we studied the folding of a set of
homologous all-{\alpha} proteins and found that nonnative-contact-based
energetic frustrations are closely related to protein native-contact networks.
In this paper, we studied the folding of nine homologous immunoglobulin-like
(Ig-like) \b{eta}-sandwich proteins and examined energetic frustrations caused
by nonnative inter-residue interactions, based on analyses of residual
phi-values and contact maps of transition state ensembles. The proteins share
similar tertiary structures, thus minimize topology frustration differences in
protein folding and highlighting the effects of energetic frustrations as
caused by hydrophilic-hydrophobic mutations. Our calculations showed that
energetic frustrations have highly heterogeneous effects on the folding of most
secondary structures and on the folding correlations between different
folding-patches of \b{eta}-sandwich proteins. The simulations revealed a strong
interplay between energetic frustrations and native-contact networks in
\b{eta}-sandwich domains, which ensures that \b{eta}-sandwich domains follow a
common folding mechanism. Our results suggested that the folding processes of
\b{eta}-sandwich proteins might be redesigned by carefully manipulating
energetic frustrations at residue level.